The Molecular Mechanisms of the N-cadherin and the Wnt/β-catenin Pathway Facilitate Drug Resistance in Leukemia Stem Cells and Mesenchymal Stem Cells
[Objective]To explore the molecular mechanisms of the N-cadherin and the Wnt/β-catenin pathway facilitate drug resistance in leukemia stem cells(LSC)and mesenchymal stem cells(MSC).[Meth-ods]The study included 65 patients with acute myeloid leukemia(AML),of whom 41 achieved complete re-mission(CR group)and 24 did not(non-remission,NR group).The expression of N-cadherin in CD34+CD38-stem cells was compared between these two groups.The CD34+CD38-Kg1a cells were further divided into six groups based on different treatments with MSC or idarubicin(IDA)that cell proliferation,apoptosis,and levels of N-cadherin and β-catenin were assessed.The cell adhesion and anti-apoptotic capabilities were also evaluated.[Results]The N-cadherin expression in the NR group compared was significantly higher than that in the CR group(P＜0.01).The apoptosis rate in the LSC+IDA group(Group B)was significantly higher than that in the LSC and MSC co-culture+IDA group(Group D)(P＜0.05).At IDA concentrations of 100 and 200 nmol/L,the proliferation inhibition rate in Group B was significantly higher than that in Group D(P＜0.05).The colony formation rate in Group B was significantly lower than that in Group D(P＜0.05).The Western blot results showed that the expression levels of both N-cadherin and β-catenin were higher in direct co-culture condition of MSC than in solo cultures or non-contact co-cultures.In co-culture condition with MSC,LSC showed increased expression levels of N-cadherin and β-catenin,along with an increase in nuclear β-cate-nin level.[Conclusion]MSCs in the bone marrow microenvironment can support the proliferation of LSC through N-cadherin-mediated adhesion and promote the activation of the Wnt/β-catenin pathway in LSC,thereby enabling them to evade the cytotoxic effects of chemotherapy.
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